Recently we have obtained pharmacologic evidences in rats that certain neuropeptides such as bombesin-like peptides, Beta-endorphin and TRH, act within the brain to influence markedly the ulcerogenic response to restraint stress and basal and stimulated gastric acid secretion. The research project will constitute an attempt to further establish the role of endogenous brain peptides as chemical messengers participating in the CNS modulation of gastric secretion under physiologic and pathologic circumstances and to further elucidate their mechanism of action. The research plan will focus on 4 major questions: 1) Localization in rat brain of the sites of peptide action using stereotaxic microinjection techniques in various brain areas. 2) Characterization of the neurohumoral pathways from the CNS to the gut through which peptides injected into the brain exert a stimulatory or inhibitory effect on gastric secretion. The methodology will involve surgical lesions and pharmacological selective blockage of various neurohumoral transmitters and specific RIA measurement of peptide (Gastrin, somatostatin) variations in plasma and tissues. 3) Extension of our observations carried out in rats to dogs. The study will include the effects of intracerebroventricular injection of bombesin and TRH in mongrel dogs on gastric secretion. 4) Role of endogenous neuropeptides on changes in gastric secretion induced by neurogenic stimuli (stress, sham feeding), using passive immunization with specific antiserum injected locally into specific brain sites and desensitization techniques. Variations in gastric volume, acidity, pepsin, mucus, and bicarbonate secretion will be monitored. Such studies could have important new implications for our understanding of the mechanisms through which neurogenic stimuli affect gastric secretion in mammals and how the brain could initiate dysfunction of gastric secretion leading to peptic ulcer and other diseases.